Tag Archives: Microbiome

Changes in Gut Microbiome Associated with MS Treatment

As the most widespread disabling neurological condition in young adults, multiple sclerosis (MS) affects approximately 1 million people in the United States and up to 2.3 million across the globe. Although researchers have not yet discovered the underlying causes of the condition or the reasons behind its unpredictable progression, there is an increased focus on the role of the gut microbiome in its development.

Prior research linking gut flora and multiple sclerosis has shown differences in the types of gut bacteria found in individuals with multiple sclerosis (MS). Patients with MS tend to have more archea –  a microbe responsible for inflammation – and less butyricimonas – a microbe with anti-inflammatory properties – compared with individuals without the condition.

New research implicates that patients with multiple sclerosis exhibit changes in gut bacteria composition after being treated with the disease-modifying drug ocrelizumab (Ocrevus).

Effect of Medication on Gut Microbiome

Disease-modifying medications tackle MS by depleting B cells, leading researchers to hypothesize that ocrelizumab could normalize the phenotype and metabolic profiles of gut bacteria thereby promoting an anti-inflammatory immune environment. As part of the ongoing trial, the research team is enrolling patients with new-onset multiple sclerosis and evaluating longitudinal samples of paired blood and stool with advanced techniques – including IgA-Seq, a novel tool that allows the differentiation of immune-reactive bacteria from IgA-uncoated bacteria.

Changes in Gut Bacteria

According to preliminary findings from the ongoing study, the normalization of certain components of the fecal microbiome in MS patients occurred at 1 month after ocrelizumab treatment, compared with baseline measurements. The team’s initial results are based on a cohort of 8 patients with MS and 5 control group participants.

Several members of the MS group showed very high IgA-coated indices for selected bacteria in the butyrate-producing Lachnospiraceae family at baseline. Following ocrelizumab treatment, these patients showed a reduction in the IgA coating index for butyrate producers. Furthermore, butyrate was significantly decreased at baseline in the MS group compared with levels found in the healthy control group. However, these changes did not last and the difference in butyrate levels dissipated after treatment was ceased. No differences were observed in acetate and propionate values.

Implications of Bacteria Changes

“Our data suggest that a subset of butyrate-producing gut bacteria is recognized as pathogenic by the immune system of untreated MS patients, based on high levels of IgA coating,” the researchers told Medscape Medical News, “This phenomenon could impact the amount of butyrate produced and affect the differentiation of circulating immune cells.”

The reduction of the IgA coating index of butyrate-producing bacteria as a result of ocrelizumab treatment points to its potentially significant role in the efficacy of B-cell depletion in MS patients. “The data also suggest that “changes in the gut microbiota may comprise part of the mechanism of action for a variety of MS disease-modifying therapies, including ocrelizumab,” lead author Erin Longbrake, MD, PhD told Medscape Medical News.

Due to the small scale of the study, its results are difficult to generalize; however the preliminary findings add to a growing body of evidence supporting the critical relationship between the gut microbiome and multiple sclerosis pathology. The research team is currently enrolling additional participants to investigate this connection further and plans on expanding its analysis to include long-amplicon sequencing and metabolomic analysis.

With about 200 new cases of multiple sclerosis diagnosed per day in the United States, there is an acute need for a better understanding of its underlying mechanisms. Identifying how these changes in the gut microbiome occur and improving the understanding of the implications of pharmacologic therapies could lead to the development of more targeted, personalized interventions aimed toward correcting specific pathologic modifications.

The Connection Between the Gut and Mental Health

In the past few years, the connection between the brain, gut, and microbiome has become an increasingly examined topic in the medical research community. As more research continues to prove this bidirectional link, there is a growing awareness of the importance of gut health not just for gastrointestinal health but also for overall physical and mental wellbeing. Studies of the connection between the gut and physical health have revealed the powerful effects of the microbiome on the immune system, mood, energy levels, and a range of other bodily aspects.

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The Gut Microbiome & Its Influence

While scientists remain uncertain about the specific causes of rheumatoid arthritis, an emerging body of research has led many to suspect that the microbiome—the bacteria that live in the gastrointestinal tract—may be to blame.

Rheumatoid arthritis occurs when the body attacks its own joints: several recent studies have found additional correlations between gut microbes and other diseases in which the body’s immune system goes ‘awry,’ and begins to attack its own tissue.

In 2013, Jose Scher, a rheumatologist at New York University, published a study that found people with rheumatoid arthritis were far more likely to have a bug called Prevotella copri in their intestines than people without the disease. Another study two years later indicated that aptients with psoriac arthritis, another type of autoimmune joint disease, had significantly lower levels of other types of intestinal bacteria.

Scher’s work is part of a growing effort by researchers across the globe to understand the ways in which the microbiome affects overall health. The gut contains up to one thousand different species of bacteria, which collectively weight between one and three pounds. This mass contains trillions of cells, more than the number of cells that make up our bodies. Throughout the past several years, scientists have compiled a growing collection of evidence that confirms links between these bugs and overall wellness.

These microbes can directly affect the immune system, even with diseases not located in the gut. An immunologist at the Mayo Clinic, Veena Taneja, has found striking differences in the bacterial populations of mice bred to be genetically prone to rheumatoid arthritis. Scher, director of NYU’s Microbiome Center for Rheuamtology and Autoimmunity, believes this is “frontier stuff…a shift in paradigm. By including the microbiome, we’ve added a new player to the game.”

Other research has focused on the influence of these bacteria on the immune system, as recent decades have seen a spike in the incidence of many autoimmune diseases. Several researchers state that this rise is, at least partially, due to changes in our bacterial ecosystem: altered diet, the proliferation of antibiotic use, and decreasing contact with the ‘microbe-packed natural world of animal plants’ have transformed the bacteria. NYU microbiologist Martin Blaser argues that because we lose microbes with each generation, “They are going extinct. These changes have consequences.”

Blaser’s own research has pinpointed the gut bacteria of U.S. children, finding that a specific species of bacteria thought to reduce the risk of asthma was very low. The decline of this bacteria in the West, as opposed to its appearance in the vast majority of the developing world, could have medical consequences. Blaser suspects that asthma is one of the primary illnesses affected by the changing microbiome; rates have escalated in the U.S. for the past three decades, growing over 28 percent between 2001 and 2011.

Dozens of researchers are looking into a range of potential strategies to use bacteria as medicine for immune disorders. Scher believes that eventually, it will be possible to treat arthritis, and other immune disorders, by adjusting the microbiome. At the Mayo Clinic, Taneja has found that a species of bacteria can prevent or halt the mouse versions of both rheumatoid arthritis, and multiple sclerosis—an autoimmune disease of the brain and nerves. Harvard University microbiologist Dennis Kasper, who discovered a targeted compound in the gut that protects mice from certain autoimmune diseases, including MS, is optimistic: “In 10 or 15 years, I think the microbiome will be a key therapeutic option for some of these diseases. There will be challenges, but I don’t see why it can’t happen. This isn’t science fiction.”